Here we go: --- ADRENAL NEOPLASMS — Adenoma vs Carcinoma Feature Adenoma Carcinoma --- --- --- Size Small, 100g Gross Yellow, well-circumscribed, smooth Grey-wh
ADRENAL NEOPLASMS — Adenoma vs Carcinoma Feature Adenoma Carcinoma --- --- --- Size Small, 100g Gross Yellow, well-circumscribed, smooth Grey-white, irregular, necrotic Histology Uniform clear cells, thin capsule, no invasion Pleomorphic cells, mitoses, necrosis, vascular invasion Capsule Intact Breached — invasion is diagnostic Metastasis No Yes — only reliable criterion of malignancy alongside invasion CDC73/parafibromin Intact Mutated in ~70% ACTH Suppressed (autonomous cortisol) Suppressed Prognosis Excellent after adrenalectomy Poor — local recurrence in 1/3, distant metastasis in 1/3 ⚠️ Key point: Cytology alone cannot diagnose carcinoma. Only vascular invasion , capsular invasion , or metastasis confirms malignancy. MEN SYNDROMES (Multiple Endocrine Neoplasia) Feature MEN1 MEN2A MEN2B --- --- --- --- Gene MEN1 (chromosome 11q13, tumour suppressor) RET proto-oncogene RET proto-oncogene Parathyroid Hyperplasia/adenoma ✅ Hyperplasia ✅ No Pancreas Islet cell tumours (gastrinoma, insulinoma) ✅ No No Pituitary Adenoma (prolactinoma most common) ✅ No No Adrenal No Phaeochromocytoma ✅ Phaeochromocytoma ✅ Thyroid No Medullary thyroid carcinoma ✅ Medullary thyroid carcinoma ✅ Other — — Marfanoid habitus, mucosal neuromas Mnemonic: MEN1 = 3 Ps — P arathyroid + P ancreas + P ituitary MEN2A = 2 Ps — P arathyroid + P haeochromocytoma + medullary thyroid MEN2B = Phaeochromocytoma + medullary thyroid + marfanoid/neuromas (no parathyroid) ⚠️ Key points: MEN1 mutation is found in 30–35% of sporadic parathyroid adenomas. A RET mutation in MEN2 necessitates screening family members and considering prophylactic thyroidectomy in carriers. Always screen phaeochromocytoma patients for MEN2. PARATHYROID CELL TYPES Cell Type Size Cytoplasm Function Granules --- --- --- --- --- Chief cells 12–20 μm, predominant Light to dark pink, polygonal PTH synthesis and secretion PTH secretory granules present Oxyphil cells Larger than chief cells Deeply eosinophilic, packed with mitochondria Unknown (transitional/inactive) Sparse/absent secretory granules Key points: Chief cells predominate and are the primary functional cells responsible for PTH synthesis and secretion . Oxyphil cells increase with age, typically appearing after puberty. Their exact function remains unknown, but they are thought to be transitional or inactive. Stromal fat within the parathyroid gland increases up to age 25, then plateaus at approximately 30% of the gland's volume. Adenomas are mostly composed of chief cells , with oxyphil adenomas being rare. Water-clear cell hyperplasia is characterized by glycogen-rich clear cells and is observed in some forms of hyperplasia. RENAL TUBULAR ACIDOSIS (RTA) Definition: Renal tubular acidosis (RTA) is characterized by a defect in renal acid-base handling, leading to a normal anion gap metabolic acidosis despite normal or near-normal glomerular filtration rate (GFR). Feature Type 1 (Distal) Type 2 (Proximal) Type 4 --- --- --- --- Defect Impaired H⁺ excretion in collecting duct Impaired HCO₃⁻ reabsorption in proximal tubule Hypoaldosteronism → impaired H⁺ and K⁺ excretion Urine pH Always 5.5 (cannot acidify) 5.5 Serum K⁺ ↓ Hypokalaemia ↓ Hypokalaemia ↑ Hyperkalaemia Serum HCO₃⁻ Very low Moderately low Mildly low Causes Sjögren's, SLE, amphotericin B, medullary sponge kidney Fanconi syndrome, multiple myeloma, Wilson's disease Diabetic nephropathy, ACEi/ARBs, Addison's disease Complications Nephrocalcinosis, nephrolithiasis, osteomalacia Rickets/osteomalacia Arrhythmias from hyperkalaemia Treatment Oral bicarbonate (small doses) Large oral bicarbonate + treat cause Fludrocortisone, dietary K⁺ restriction ⚠️ Key distinguishing point: Type 4 is the only RTA with hyperkalaemia ; all other types present with hypokalaemia. Type 4 is also the most common RTA encountered in clinical practice, frequently associated with diabetic nephropathy . DIABETIC NEPHROPATHY — Pathogenesis & Morphology Pathogenesis (stepwise): The pathogenesis of diabetic nephropathy begins with chronic hyperglycaemia , which leads to the glycation of proteins and the formation of Advanced Glycation End-products (AGEs) , resulting in mesangial expansion . Concurrently, hyperglycaemia causes an increase in intraglomerular pressure due to afferent arteriole dilation exceeding efferent arteriole constriction, leading to hyperfiltration and subsequent glomerular hypertension . This hypertension contributes to glomerular basement membrane (GBM) thickening , marking the onset of proteinuria , initially as microalbuminuria . As the disease progresses, there is further mesangial expansion, culminating in nodular glomerulosclerosis , specifically the formation of Kimmelstiel-Wilson nodules . Ultimately, diffuse glomerulosclerosis leads to a decline in GFR, progressing to Chronic Kidney Disease (CKD) and eventually End-Stage Renal Disease (ESRD) . Morphology: Diffuse glomerulosclerosis: This is the most common finding, characterized by a uniform expansion of the mesangial matrix. Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules): These are ovoid or spherical nodules of acellular matrix typically found in the periphery of the glomerulus and are pathognomonic of diabetic nephropathy . GBM thickening: A characteristic feature observed early in the disease. Hyaline arteriolosclerosis: Affects both the afferent AND efferent arterioles , with efferent involvement being unique to diabetes. Exudative lesions: Include hyaline caps and capsular drops. Clinical progression: 1. Stage 1: Hyperfiltration — Characterized by an increased GFR with no proteinuria. 2. Stage 2: Silent — Involves GBM thickening and other microstructural changes, but remains clinically asymptomatic. 3. Stage 3: Microalbuminuria (30–300 mg/day) — This is the earliest clinical sign of diabetic nephropathy. 4. Stage 4: Macroalbuminuria ( 300 mg/day) — Accompanied by a decreased GFR and the development of hypertension. 5. Stage 5: ESRD — Requires dialysis or kidney transplant. ⚠️ Key points: Microalbuminuria is the earliest detectable clinical sign of diabetic nephropathy . ACE inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs) slow disease progression by reducing intraglomerular pressure through dilation of the efferent arteriole. Hyalinosis affecting both afferent and efferent arterioles is unique to diabetic nephropathy, distinguishing it from hypertensive nephropathy, which typically affects only the afferent arteriole.